β-Catenin mutations in pulmonary blastomas: association with morule formation

• Published in: The Journal of pathology 2003-06, Vol.200 (2), p.214-221
• Main Authors: Sekine, Shigeki, Shibata, Tatsuhiro, Matsuno, Yoshihiro, Maeshima, Arafumi, Ishii, Genichiro, Sakamoto, Michiie, Hirohashi, Setsuo
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Adenocarcinoma, Clear Cell - genetics; Adenocarcinoma, Clear Cell - metabolism; Adenocarcinoma, Clear Cell - pathology; Adult; Aged; beta Catenin; Biological and medical sciences; Cytoskeletal Proteins - genetics; Cytoskeletal Proteins - metabolism; Diagnosis, Differential; DNA Mutational Analysis - methods; DNA, Neoplasm - genetics; Female; Humans; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Male; Medical sciences; Middle Aged; Morula - pathology; morule; Mutation; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; neuroendocrine cells; Pneumology; pulmonary blastoma; Pulmonary Blastoma - genetics; Pulmonary Blastoma - metabolism; Pulmonary Blastoma - pathology; Trans-Activators - genetics; Trans-Activators - metabolism; Tumors of the respiratory system and mediastinum; well-differentiated fetal adenocarcinoma; β-catenin
• ISSN: 0022-3417; 1096-9896
• DOI: 10.1002/path.1352

To elucidate the contribution of β‐catenin gene mutation to the development of pulmonary blastomas, we analysed mutations in three well‐differentiated fetal adenocarcinomas (WDFAs) and six biphasic pulmonary blastomas (BPBs). For comparison, eight clear‐cell adenocarcinomas with fetal lung features were also examined. β‐Catenin gene mutations were found in all three WDFAs, two BPBs, and none of the clear‐cell adenocarcinomas with fetal lung features. All tumours with mutations had a common histological feature, namely morule formation, and showed a characteristic heterogeneous β‐catenin expression pattern that was revealed by immunohistochemistry. Strong nuclear/cytoplasmic expression of β‐catenin was seen in clustered cells in the morular areas and in single cells in glands, and was associated with neuroendocrine differentiation. As β‐catenin mutations are rare among lung tumours, this distinctive genetic feature, which is also immunohistochemically detectable as overexpression with a heterogeneous pattern, has diagnostic significance. The presence of this common genetic alteration found in both WDFA and BPB implies a histogenetic linkage between these tumours. Copyright © 2003 John Wiley & Sons, Ltd.